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4: Delirium and Viral Encephalitis > Lecture: Immune System and the Nervous System > Flashcards

Lecture: Immune System and the Nervous System Flashcards

1
Q

What is delirium?

A

• Clinical syndrome (a set of symptoms) of early brain or mental dysfunction
Precipitated by:
• medical illness
• substance intoxication/withdrawal
• medication side-effect
Can effect a patients thinking and result in reduced awareness of environment.

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2
Q

How is delirium diagnosed

A

Clinical diagnosis

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3
Q

Describe the three cardinal features of delirium

A

• Conscious state is altered: Stupor/ drowsiness vs hypervigilance/ agitation
• Cognitive impairment: Inattention, disorientation, global cognitive impairment Inability to focus
• Course: Fluctuating with an acute onset
Duration hours to days

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4
Q

What are three important differentials for delirium?

A

Differential diagnosis: important in distinguishing between a number of psychiatric
disorders as signs and symptoms are also present in
• Dementia
• Depressive disorders
• Schizophrenia

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5
Q

Describe typical symptoms of hyperactive delirium

A

Hyperactive
• psychomotor agitation, restlessness, anxiety, labile affect, verbal aggression, visual hallucinations
• Example: mania, psychosis but no previous history of psychiatric illness

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6
Q

Describe typical symptoms of hypoactive delirum

A

Hypoactive
• Somonlence, decreased attention span, withdrawn
• Example: withdrawn delirium – major depressive disorder. Can be misdiagnosed.
• MDD: cognitive symptoms but normal consciousness

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7
Q

What are some typical symptoms of delirium?

A
  • Cognitive deficits (including attention, orientation, memory, visuoconstruction and executive functions)
  • An acute onset
  • Sleep/wake cycle disturbance (including cycle reversal)
  • Abnormal affect (labile, irritable, agitation, restlessness, aggression, apathetic)
  • Impairment of psychomotor behaviour
  • Psychotic symptoms (hallucinations, fleeting delusions and thought disorder)
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8
Q

Describe alcohol tremens and common symptoms

A
  • Severe alcohol withdrawal, with the following clinical features:
  • Delirium
  • Autonomic hyperactivity (diaphoresis, tachycardia, hypertension)
  • Hypervigilance, agitation
  • Tremors
  • Often with hallucinations (esp. visual & tactile)
  • Increased risk of alcohol withdrawal seizures & death
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9
Q

Describe some adverse effects delirium is associated with

A

Associated with the following:
•  mortality
•  risk of cognitive & functional decline
•  hospital length of stay
•  nursing care
•  likelihood of needing residential placement
•  post-operative recovery/rehabilitation

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10
Q

Predisposing factors to delirium?

A 
Advanced age
Sensory impairment
Poly pharmacy
Cognitive/functional impairment
History of delirium
Medications:
- psychoactive drugs
- anticholinergic drugs
- alcohol abuse
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11
Q

Precipitating factors for delirium?

A 
Drugs
- polypharmacy
- sedating drugs
- anticholinergic drugs
- substance intoxication or withdrawal
Toxins
Surgery
Anaesthetics
Critical Illnesses
- neurological conditions (head trauma,
tumor, cranial hypertension)
- infections (respiratory, UTI)
- hypoxia
- metabolic/electrolyte disturbances
- febrile illness
- urinary retention/ constipation
- pain
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12
Q

Outline the pathophysiology of delirium

A

Unclear
Functional imaging
• Generalised disruption of higher cortical function

Multiple pathways affected:
• Neurotransmission (cholinergic deficiency, monoaminergic disturbances)
• Physiological stress
• Oxidative metabolism
• Circadian rhythm (Sleep-wake cycle - maintenance of memory circuits)
• Patient losses orientation
• Limbic system
• Immune system - neuroinflammation
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13
Q

What is psychosis?

A

A loss or break from reality. Clinical diagnosis NOT a disorder arising from abnormal brain functions.
• Characterised by fundamental distortions of thinking, perception and
emotional response
• Causes an individual to lose contact with reality during the active stages of
the syndrome– 4.5% of population
• Typically occurring late teens or early adulthood and can be recurring or
chronic
• Approx 1 in 100 people will experience psychosis in their lifetime and 1 in
4 will meet criteria for psychotic disorder
• A psychotic illness includes schizophrenia, bipolar disorder, schizoaffective
disorder and delusional disorder

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14
Q

Early warning signs of psychosis?

A

Depression, anxiety, feeling off, feeling as if thoughts have sped up or slowed down

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15
Q

What are the key features of psychosis?

A 
Faculties of mental capacity that are altered during psychosis such as:
Thoughts (delusions)
Mood & 
Feelings Volition
Cognition (memory, attention)
Perceptions (Hallucinations)

These thoughts can lead to ALTERED BEHAVIOUR

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16
Q

Difference symptoms in primary and secondary psychosis?

A

No specific characteristic for either primary or secondary psychosis

17
Q

Outline the diagnostic workup for psychosis

A
  • Screen broadly
  • Thorough history and examination
  • Focus on a thorough neurological examination
  • Mental state examination
  • Bloods
  • CBE, Glucose, Electrolytes, LFTs, BAC, CRP/ESR
  • Neuroimagining
  • CT scan or MRI
  • CXR
  • Exclude specifically if suggested
  • Abnormal levels of TSH, TFT, vitamin B12 and folate, Syphilis/ HIV serology, FTA-Abs
  • Investigate further as clinically indicated
  • Electroencephalogram (EEG within a few weeks of presentation)
  • Chest radiography, lumbar puncture, blood and urine cultures, arterial blood gases
  • Serum cortisol levels
  • Toxin search
  • Drug levels eg urine drug screen
  • Genetic testing
18
Q

Main differentiating factors between Delirium and Psychosis

A

Pattern/course is more stable in p and fluctuating in d
Attention is delusion in p and disordered in d
Cognition is selectively impaired in p and disordered in d

19
Q

Diagnostic criteria for Schizophrenia?

A

A. Two or more of the following, each
present for 1 month (or less if
successfully treated). At least one of
these must be (1), (2), or (3):

  1. Delusions
  2. Hallucinations
  3. Disorganised Speech
  4. Grossly disorganised or catatonic behaviour
  5. Negative symptoms

B. Decline in one or more major areas of
functioning.

C. Continuous disturbance for at least 6
months.
Exclusion of mood or schizoaffective
disorders, substance, general medical
condition, or pervasive developmental
disorder.
20
Q

positive symptoms of schizophrenia?

A

Psychotic (distortion of reality)

  • Hallucinations
  • Delusions
  • Catatonia
21
Q

negative symptoms of schizophrenia?

A

Negative (Deficit) Symptoms

  • avolition (disinterest, ambivalence)
  • anhedonia (reduced experience of pleasure)
  • Apathy (social withdrawal)
  • affective (emotional) blunting
  • Alogia (poverty of speech)
22
Q

disorganised symptoms of schizophrenia?

A
  • Formal thought disorder (disorganised thoughts, manifested by disjointed speech)
  • Disorganised behaviour and inappropriate affect (eg smiling when discussing a sad event)
  • Bizzare behaviours
23
Q

Neurocognitive symptoms of schizophrenia?

A
  • Common
  • (overlaps with negative symptoms)
  • Poverty of thought content
  • Affects frontal lobe tasks – executive functions
  • Associated with impairment in work and social functioning
24
Q

Aetiological factors of schizophrenia?

A

• Multidimensional with genetic and environmental factors interacting: GxE

Genetic causative factors

  • 80% heritability estimate
  • monozygotic twins 50% concordant for schizophrenia

Environmental causative factors
- Prenatal and perinatal stressors
- Infectious agents
- Childhood and adulthood trauma
- Substance use
• Associations vary between person to person – heterogeneity
• Associated range of structural and functional brain abnormalities
• Variable longitudinal course – 40% having significant long term disability

25
Q

Prevalence of schizophrenia

A

1 in 100

26
Q

How is schizophrenia treated?

A

antipsychotics. Antagonise mono adrenergic pathways. Reduce hypersensitivity to dopamine.

27
Q

What percentage of patients are resistant to antipsychotic treatment for schizophrenia?

A
  • Treatment resistance:
  • Up to 1/3 of patients fail to respond to antipsychotic medication
    e. g. ( no effect on cognition)
  • After 2 failed trials (4-8 wks each), clozapine is indicated
  • Severe refractory cases; ECT is an option
28
Q

Side effects of antipsychotics?

A
  • Common anti-psychotic side effects:
  • Metabolic syndrome
  • Sexual dysfuction
  • Prolactin elevation
  • QTc prolongation
  • Extrapyramidal side effects
29
Q

Empirical evidence for inflammation associated depression

A
  1. Elevated immune signalling mediators
    • elevated levels of circulating granulocytes, monocytes and acute phase proteins, immune signalling molecules such as CRP, IL_1b, IL_6, TNFa compared to healthy controls and pronounced
    in suicide attemptees .
    • Also chemokines, prostaglandins, adhesion molecules.
  2. Immune stimulating therapies
    • 30-40% non-depressed melanoma/cancer or hepatitis C patients receiving immune stimulating IL_2 or IFNa develop depression (Denicoff 1987, Renault
    1987) associated with increased IL_6 (Raison 2009)
  3. Exogenous administration of immune signalling mediators
    • Conversely experimental healthy animals demonstrate sickness behaviour post exogenous administration of IL_1b or TNFa
  4. Anti-depressants
    • Certain classes of anti-depressants exert anti-inflammatory effects (Hannestad 2011)
    • eg selective serotonin reuptake inhibitors (SSRIs) can block effects of inflammatory cytokines on the
    brain
  5. Anti-inflammatories
    • Conversely certain anti-inflammatories exert anti-depressive effects eg treatment with anti-TNFa antagonist (Infliximab) or aspirin in combination with minocycline
    (Savitz 2013)
  6. Gene association
    • GWAS studies show links between certain gene variants (Caspi and mood disorders this means
    differential gene expression between people with depression and those without (Savitz 2012) as are
    abnormal alleles of IL_1b and TNF genes in treatment resistant MDD patients (Ma Li Wong 2008)
  7. Epidemiological association
    • an epidemiological association exists between MDD and disorders with an inflammatory or autoimmune
    component such as MS, type 2 diabetes (Nouwen 2010) or cardiovascular disease (Van der Kooy 2007)
30
Q

Evidence for Neuroinflammation as underlying

cause for pathophysiology of schizophrenia

A

Increased number of circulating monocytes
– enhanced gene expression of immune genes

Elevated monocyte/macrophage related pro inflammatory cytokines in CSF and periphery plasma/serum: IL-1, IL-6, TNFa, CRP

• Antipsychotic effects by anti-inflammatory drugs such
as NSAIDs and minocycline

• Microglial activation revealed by PET scans/ histopathology in brains from SCZ patients

4: Delirium and Viral Encephalitis (3 decks)

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